The electrophysiology section of this core will screen conotoxins for their functional activities against known ion channel targets as well as identify possible new targets for novel conotoxins. The anatomy section of the Core will identify the sites of conotoxin binding in mammalian brain by autoradiography following exposure to 125I-labeled conotoxins. These anatomical experiments assessing the binding of toxins to their targets will complement the physiological experiments assessing the toxins' effects on target function. 1. OBJECTIVES 1. Qualitative screening of conotoxins for their effects on known ion channel targets, both voltage-and ligand-gated. 2. Quantitative determination of the potencies of toxins (and derivatives) in affecting their targets' function. A given toxin's ability to affect a given class of ion channels can differ depending on the specific tissue, cell type, or species of animal wherein the channel resides, so comparative pharmacology can be involved. When appropriate, kinetic, in addition to equilibrium, constants will be determined. 3. Identification of the locations of the binding sites of the conotoxins within the mammalian CNS, and characterization of the affinity of these sites for toxin. 4. Identification and characterization of new targets for novel toxins.